成年期甲状腺功能减退症大鼠额叶突触结合蛋白I表达及T4替代治疗作用

目的 观察成年期甲状腺功能减退症(甲减)大鼠额叶突触结合蛋白I(synaptotagmin I,sytI)表达改变及不同剂量甲状腺素替代治疗的作用.方法 将44只大鼠按体质量随机分为甲减组、常规治疗组、大剂量治疗组、对照组,用丙基硫氧嘧啶(PTU)腹腔注射建立成年期大鼠甲减及治疗模型;放射免疫法测定4组大鼠血清甲状腺激素水平,免疫组织化学S-P法分析sytI蛋白在4组大鼠额叶分子层、外颗粒层、外锥体细胞层、内颗粒层、内锥体细胞层中的表达.结果 甲减组大鼠血清T3、T4[(0.34±0.04)、(43.01±2.95)nmol/L]显著低于对照组[(0.65±0.15)、(55.20±3.56)nmol/L,F值分别为6.026、4.503,P<0.05或<0.01],甲减组鼠syt I免疫反应产物在额叶分子层(0.018±0.010)、外颗粒层(0.020±0.007)、外锥体细胞层(0.013±0.008)、内颗粒层(0.011±0.005)、内锥体细胞层(0.024±0.013)均较对照组(0.028±0.010、0.031±0.010、0.028±0.010、0.022±0.008、0.038±0.013)明显减少(F值分别为5.697、8.965、14.668、13.597、6.807,P<0.05或<0.01).常规治疗组大鼠血清T3、T4[(0.63±0.05)、(55.04±3.77)nmoL/L]与对照组比较,差异无统计学意义(F值分别为3.162、0.367,P均>0.05),额叶分子层、外颗粒层、外锥体细胞层、内颗粒层、内锥体细胞层syt I蛋白表达(0.027±0.013、0.025±0.009、0.022±0.008、0.020±0.010、0.033±0.010)与对照组比较差异均无统计学意义(F值分别为0.094、2.208、2.467、0.350、0.693,P均>0.05);大剂量治疗组大鼠血清T3、T4[(1.11±0.10)、(96.68±6.42)nmol/L]显著高于对照组(F值分别为6.291、12.031,P均<0.01),额叶各层syt I蛋白表达(0.028±0.008、0.031±0.011、0.026±0.012、0.023±0.011、0.038±0.010)与对照组比较的差异均无统计学意义(F值分别为0.001、0.019、0.111、0.061、0.001,P均>0.05).结论 成年期甲减大鼠额叶内syt I蛋白表达减少,常规剂量甲状腺素替代治疗就能使其恢复至正常水平.     

Transient hypothyroxinemia in juvenile glycoprotein hormone subunit B5 knock-out mice

The heterodimer thyrostimulin, comprised of two novel glycoprotein hormone subunits GPA2 and GPB5, activates the TSH receptor. To understand its role in the regulation of the hypothalamus–pituitary–thyroid (HPT-) axis, we evaluated juvenile and adult GPB5 knock-out (GPB5^−/−) and wild type mice (WT) during euthyroidism, hypothyroidism and thyrotoxicosis. Surprisingly, juvenile euthyroid GPB5^−/− mice displayed marked hypothyroxinemia (25% lower serum T₄, unchanged TSH) and also during thyrotoxicosis juvenile GPB5^−/− mice had 25% lower serum T₄, compared to WT. During hypothyroidism, despite similar serum T₄, pituitary TSHβ mRNA was 2-fold lower in GPB5^−/− mice compared to WT. Adult mice displayed increased pituitary deiodinase type 2 during euthyroidism and decreased serum T₄ during hypothyroidism in GPB5^−/−. Thus, lacking GPB5 results in moderate deviations of the HPT-axis. The more pronounced differences observed in juvenile mice compared to adult mice are in agreement with the notion that GPB5 has a role during development.     

Marginal iodide deficiency and thyroid function: dose-response analysis for quantitative pharmacokinetic modeling

Severe iodine deficiency (ID) results in adverse health outcomes and remains a benchmark for understanding the effects of developmental hypothyroidism. The implications of marginal ID, however, remain less well known. The current study examined the relationship between graded levels of ID in rats and serum thyroid hormones, thyroid iodine content, and urinary iodide excretion. The goals of this study were to provide parametric and dose-response information for development of a quantitative model of the thyroid axis. Female Long Evans rats were fed casein-based diets containing varying iodine (I) concentrations for 8 weeks. Diets were created by adding 975, 200, 125, 25, or 0 μg/kg I to the base diet (∼25 μg I/kg chow) to produce 5 nominal I levels, ranging from excess (basal + added I, Treatment 1: 1000 μg I/kg chow) to deficient (Treatment 5: 25 μg I/kg chow). Food intake and body weight were monitored throughout and on 2 consecutive days each week over the 8-week exposure period, animals were placed in metabolism cages to capture urine. Food, water intake, and body weight gain did not differ among treatment groups. Serum T4 was dose-dependently reduced relative to Treatment 1 with significant declines (19 and 48%) at the two lowest I groups, and no significant changes in serum T3 or TSH were detected. Increases in thyroid weight and decreases in thyroidal and urinary iodide content were observed as a function of decreasing I in the diet. Data were compared with predictions from a recently published biologically based dose-response (BBDR) model for ID. Relative to model predictions, female Long Evans rats under the conditions of this study appeared more resilient to low I intake. These results challenge existing models and provide essential information for development of quantitative BBDR models for ID during pregnancy and lactation.     

矮小儿童甲状腺功能改变与尿碘关系的探讨

目的:探讨碘摄入与甲状腺功能的关系,以期指导临床合理补碘.方法:2010年1～2月因身材矮小收入我院内分泌科进行相关检查的患儿为研究对象,依据甲状腺功能情况分为3组:亚临床甲减组(SCH组)、临床甲减组(CH组)和甲状腺功能正常组(正常组);所有病例进行甲状腺功能、晨起空腹尿碘测定等.并对SCH组患儿进行随访.结果:1 689例矮小患儿中,碘摄入不足65例(3.8％),碘过量593例(35.2％),碘摄入正常1031例(61.1％).SCH 105例(6.2％)、CH 23例(1.4％)、正常1 586例(92.4％).105例SCH中,高尿碘78例(74.2％).高尿碘发生率SCH组显著高于CH组和正常组(P＜0.01),SCH组、CH组、正常组尿碘中位数分别为389.38μg/L、136.21 μg/L、221.52μg/L.经过饮食干预和(或)甲状腺素替代治疗3个月后,尿碘均正常7例TSH仍增高.结论:碘摄入过多可能是儿童亚临床甲减的重要原因,尿碘检测应成为儿童常规的检测项目,发现异常及时干预可减少对儿童体格和智力的影响.     

原发性甲状腺功能减低症与垂体腺瘤的鉴别诊断

目的探讨原发性甲状腺功能减低致垂体增生的临床特点和诊治方法,避免误诊。方法9例患者各经X线平片、CT、MRI等影像检查发现鞍内鞍上占位性病变,但因影像学及临床特点不典型,经内分泌检查、骨龄检查等确诊为原发性甲状腺功能减低导致垂体增生,遂采用激素替代治疗。结果9例患者均口服甲状腺片治疗,随访4~18个月,内分泌检查除TSH仍高于正常,其余均恢复正常,症状均有不同程度减轻,其中2例患者复查MRI发现病变明显缩小。结论原发甲状腺功能减低,易误诊为垂体腺瘤,应进行内分泌检查、骨龄检查等明确诊断,治疗采用激素替代治疗。     

甲状腺功能减退性心包积液超声心动图分析

目的研究甲状腺功能减退性心包积液的超声改变,并探讨超声心动图对甲状腺功能减退性心包积液的诊断价值。方法以19例甲状腺功能减退性心包积液的超声心动图改变与正常人对比。结果 19例甲状腺功能减退性心包积液组左房内径、室间隔厚度、左室后壁厚度与正常对照组比较差异有统计学意义(P<0.01),均无心包填塞发生。结论彩色多谱勒超声心动图对甲状腺功能减退性心包积液的诊断与鉴别诊断有重要意义,其中左房扩大、左室舒张功能不全多发。     

甲状腺功能异常与血脂水平相关性

目的研究甲状腺功能异常患者血脂水平紊乱的特点及甲状腺激素与血脂水平的相关性。方法根据临床诊断设甲亢组86例、甲减组67例,以正常体检人员36例为对照组,分析各组甲状腺激素与血脂水平的相关性。结果三组甲状腺激素检测指标、血脂检测指标差异均有统计学意义（均P〈0.05）;游离三碘甲腺原氨酸（FT3）、游离甲状腺素（FT4）与血脂均存在不同程度的负相关,促甲状腺素（TSH）与血脂均存在不同程度的正相关。结论甲状腺功能异常常导致脂代谢的紊乱,甲状腺激素水平与血脂水平密切相关。     

探讨孕妇不同孕期尿碘含量对新生儿甲状腺功能的影响

目的探讨孕妇在不同怀孕阶段的尿碘含量和新生儿先天性甲减之间的相关性,为制订孕妇尿碘筛查的最佳时机和科学补碘提供理论依据。方法采用过氧乙酸四甲基联苯胺氧化显色法检测妊娠妇女尿碘水平;采用荧光酶免法检测干滤纸血片中促甲状腺激素（TSH）浓度;用化学发光法测定甲状腺功能。结果孕0～12、13～20、21～28、29～35、36～41周及产后3～6 d孕妇尿碘的中位数分别为178、165、136、129、196、232μg/L;妊娠21～28、29～35周孕妇尿碘水平偏低;孕21～28周尿碘低下组孕妇TSH水平[（5.66±2.92）mU/L]明显高于尿碘正常组[（3.51±0.61）mU/L]（P〈0.01）;孕29～35周尿碘低下组孕妇TSH水平[（5.57±1.67）mU/L]高于尿碘正常组[（3.96±0.75）mU/L]（P〈0.05）;尿碘低下组孕妇所生的新生儿干血片TSH水平[（11.8±10.5）mU/L]明显高于尿碘正常组孕妇所生的新生儿TSH水平[（3.89±1.13）mU/L]（P〈0.01）;妊娠21～35周孕妇尿碘、TSH水平和新生儿TSH水平呈显著相关性。结论检测妊娠中、晚期孕妇的尿碘水平可评估其胎儿的碘营养状况。     

妊娠妇女甲状腺功能异常对胎儿的影响

妊娠期间甲状腺功能亢进与减低,对胎儿发育均有影响,且这两种疾病常见,但亚临床甲减对胎儿发育的影响及治疗近年仍存在争议,本研究就妊娠妇女甲状腺功能异常对胎儿影响的研究现状进行综述。